tbuckley/cabot-search huggingface dataset:
Optimal examined lymph node number for accurate staging and long-term survival in rectal cancer: a population-based study
Authors: Xu Guan, Shuai Jiao, Rongbo Wen, Guanyu Yu, Jungang Liu, Dazhuang Miao, Ran Wei, Weiyuan Zhang, Liqiang Hao, Leqi Zhou, Zheng Lou, Shucheng Liu, Enliang Zhao, Guiyu Wang, Wei Zhang, Xishan Wang
Journal: International Journal of Surgery (2023)

Although the recommended minimal examined lymph node (ELN) number in rectal cancer (RC) is 12, this standard remains controversial because of insufficient evidence. We aimed to refine this definition by quantifying the relationship between ELN number, stage migration and long-term survival in RC.Data from a Chinese multi-institutional registry (2009-2018) and the Surveillance, Epidemiology, and End Results (SEER) database (2008-2017) on stages I-III resected RC were analysed to determine the relationship between ELN count, stage migration, and overall survival (OS) using multivariable models. The series of odds ratios (ORs) for negative-to-positive node stage migration and hazard ratios (HRs) for survival with more ELNs were fitted using a Locally Weighted Scatterplot Smoothing (LOWESS) smoother, and structural breakpoints were determined using the Chow test. The relationship between ELN and survival was evaluated on a continuous scale using restricted cubic splines (RCS).The distribution of ELN count between the Chinese registry ( n =7694) and SEER database ( n =21 332) was similar. With increasing ELN count, both cohorts exhibited significant proportional increases from node-negative to node-positive disease (SEER, OR, 1.012, P <0.001; Chinese registry, OR, 1.016, P =0.014) and serial improvements in OS (SEER: HR, 0.982; Chinese registry: HR, 0.975; both P <0.001) after controlling for confounders. Cut-point analysis showed an optimal threshold ELN count of 15, which was validated in the two cohorts, with the ability to properly discriminate probabilities of survival.A higher ELN count is associated with more precise nodal staging and better survival. Our results robustly conclude that 15 ELNs are the optimal cut-off point for evaluating the quality of lymph node examination and stratification of prognosis.
Targeting PP2A-dependent autophagy enhances sensitivity to ruxolitinib in JAK2V617F myeloproliferative neoplasms
Authors: Charly Courdy, Loïc Platteeuw, Charlotte Ducau, Isabelle De Araujo, Emeline Boet, Ambrine Sahal, Estelle Saland, Valérie Edmond, Suzanne Tavitian, Sarah Bertoli, Pierre Cougoul, Fanny Granat, Laura Poillet, Caroline Marty, Isabelle Plo, Jean-Emmanuel Sarry, Stéphane Manenti, Véronique Mansat-De Mas, Carine Joffre
Journal: Blood Cancer Journal (2023)

The Janus kinase 2 (JAK2)-driven myeloproliferative neoplasms (MPNs) are chronic malignancies associated with high-risk complications and suboptimal responses to JAK inhibitors such as ruxolitinib. A better understanding of cellular changes induced by ruxolitinib is required to develop new combinatory therapies to improve treatment efficacy. Here, we demonstrate that ruxolitinib induced autophagy in JAK2V617F cell lines and primary MPN patient cells through the activation of protein phosphatase 2A (PP2A). Inhibition of autophagy or PP2A activity along with ruxolitinib treatment reduced proliferation and increased the death of JAK2V617F cells. Accordingly, proliferation and clonogenic potential of JAK2V617F-driven primary MPN patient cells, but not of normal hematopoietic cells, were markedly impaired by ruxolitinib treatment with autophagy or PP2A inhibitor. Finally, preventing ruxolitinib-induced autophagy with a novel potent autophagy inhibitor Lys05 improved leukemia burden reduction and significantly prolonged the mice's overall survival compared with ruxolitinib alone. This study demonstrates that PP2A-dependent autophagy mediated by JAK2 activity inhibition contributes to resistance to ruxolitinib. Altogether, our data support that targeting autophagy or its identified regulator PP2A could enhance sensitivity to ruxolitinib of JAK2V617F MPN cells and improve MPN patient care.
CimpleG: finding simple CpG methylation signatures
Authors: Tiago Maié, Marco Schmidt, Myriam Erz, Wolfgang Wagner, Ivan G. Costa
Journal: Genome biology (2023)

Abstract DNA methylation signatures are usually based on multivariate approaches that require hundreds of sites for predictions. Here, we propose a computational framework named CimpleG for the detection of small CpG methylation signatures used for cell-type classification and deconvolution. We show that CimpleG is both time efficient and performs as well as top performing methods for cell-type classification of blood cells and other somatic cells, while basing its prediction on a single DNA methylation site per cell type. Altogether, CimpleG provides a complete computational framework for the delineation of DNAm signatures and cellular deconvolution.
TREC mediated oncogenesis in human immature T lymphoid malignancies preferentially involves ZFP36L2
Authors: Estelle Balducci, Thomas Steimlé, Charlotte Smith, Patrick Villarese, Mélanie Feroul, Dominique Payet-Bornet, Sophie Kaltenbach, Lucile Couronné, Ludovic Lhermitte, Aurore Touzart, Marie-Emilie Dourthe, Mathieu Simonin, André Baruchel, Hervé Dombret, Norbert Ifrah, Nicolas Boissel, Bertrand Nadel, Elizabeth Macintyre, Agata Cieslak, Vahid Asnafi
Journal: Molecular Cancer (2023)

Abstract The reintegration of excised signal joints resulting from human V(D)J recombination was described as a potent source of genomic instability in human lymphoid cancers. However, such molecular events have not been recurrently reported in clinical patient lymphoma/leukemia samples. Using a specifically designed NGS-capture pipeline, we here demonstrated the reintegration of T-cell receptor excision circles (TRECs) in 20/1533 (1.3%) patients with T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL). Remarkably, the reintegration of TREC recurrently targeted the tumor suppressor gene, ZFP36L2, in 17/20 samples. Thus, our data identified a new and hardly detectable mechanism of gene deregulation in lymphoid cancers providing new insights in human oncogenesis.
Roles of macrophages in tumor development: a spatiotemporal perspective
Authors: Mathilde Bied, William W. Ho, Florent Ginhoux, Camille Blériot
Journal: Cellular and Molecular Immunology (2023)

Abstract Macrophages are critical regulators of tissue homeostasis but are also abundant in the tumor microenvironment (TME). In both primary tumors and metastases, such tumor-associated macrophages (TAMs) seem to support tumor development. While we know that TAMs are the dominant immune cells in the TME, their vast heterogeneity and associated functions are only just being unraveled. In this review, we outline the various known TAM populations found thus far and delineate their specialized roles associated with the main stages of cancer progression. We discuss how macrophages may prime the premetastatic niche to enable the growth of a metastasis and then how subsequent metastasis-associated macrophages can support secondary tumor growth. Finally, we speculate on the challenges that remain to be overcome in TAM research.
A comparison of cardiovascular imaging practices in Africa, North America, and Europe: two faces of the same coin
Authors: Suvasini Lakshmanan, Irina Mbanze
Journal:  (2023)

Abstract Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide. There are significant differences in the burden of cardiovascular disease and associated risk factors, across high-income countries and low- and middle-income countries. Cardiac imaging by echocardiography, cardiac computed tomography, cardiac magnetic resonance imaging, single-photon emission computed tomography, and positron emission tomography myocardial perfusion imaging are well-established non-invasive tests that aid in the diagnosis, risk stratification, and management of various cardiac diseases. However, there are significant inequalities in availability and access to imaging modalities in low- and middle-income countries attributed to financial constraints, disparities in healthcare and technical infrastructure. In the post-COVID-19 pandemic era, these disparities are exaggerated by the continued technological advancements driving innovations in the field of cardiovascular (CV) imaging in high-income countries, while there is an urgent need to provide sustainable access to diagnostic imaging for patients in economically strained healthcare systems in regions like Africa. This review aims to highlight the inequalities in the burden of cardiac disease, associated risk factors, and access to diagnostic CV imaging tests, while also exploring the need for sustainable solutions to implementing CV imaging all over the world.
Thioredoxin-1 inhibits the activation of IRE1 by targeting Hsp90/p-Cdc37 chaperone complex in Parkinson disease
Authors: Xiansi Zeng, Wenshuo Geng, Yu Zhang, Jiayi Yin, Guangtao Xu, Meng Yu, Li Li, Jinjing Jia
Journal: Ageing Research Reviews (2023)
Smart textiles for self-powered biomonitoring
Authors: Junyi Yin, Shaolei Wang, Aiden Di Carlo, Austin Chang, Xiao Wan, Jing Xu, Xiao Xiao, Jun Chen
Journal: Med-X (2023)

Abstract Merging electronics with textiles has become an emerging trend since textiles hold magnificent wearing comfort and user-friendliness compared with conventional wearable bioelectronics. Smart textiles can be effectively integrated into our daily wearing to convert on-body biomechanical, biochemical, and body heat energy into electrical signals for long-term, real-time monitoring of physiological states, showing compelling medical and economic benefits. This review summarizes the current progress in self-powered biomonitoring textiles along three pathways: biomechanical, body heat, and biochemical energy conversion. Finally, it also presents promising directions and challenges in the field, as well as insights into future development. This review aims to highlight the frontiers of smart textiles for self-powered biomonitoring, which could contribute to revolutionizing our traditional healthcare into a personalized model. Graphical Abstract Self-powered biomonitoring textiles via biomechanical, body heat, and biochemical energy conversion are discussed in this work. Platform technologies, including piezoelectric nanogenerators (PENGs), triboelectric nanogenerators (TENGs), and magnetoelastic generators (MEGs) for biomechanical energy conversion, thermoelectric generators (TEGs) for boy heat energy conversion, and biofuel cells (BFCs) for biochemical energy conversion, are systematically introduced and discussed in a textile form. Working in a self-powered manner with greatly improved wearing comfort, the smart biomonitoring textiles pave a compelling road to personalized healthcare.
Material design for oral insulin delivery
Authors: Kangfan Ji, Yuejun Yao, Xinwei Wei, Wei Liu, Juan Zhang, Yun Liu, Yang Zhang, Jinqiang Wang, Zhen Gu
Journal: Med-X (2023)

Abstract Frequent insulin injections remain the primary method for controlling the blood glucose level of individuals with diabetes mellitus but are associated with low compliance. Accordingly, oral administration has been identified as a highly desirable alternative due to its non-invasive nature. However, the harsh gastrointestinal environment and physical intestinal barriers pose significant challenges to achieving optimal pharmacological bioavailability of insulin. As a result, researchers have developed a range of materials to improve the efficiency of oral insulin delivery over the past few decades. In this review, we summarize the latest advances in material design that aim to enhance insulin protection, permeability, and glucose-responsive release. We also explore the opportunities and challenges of using these materials for oral insulin delivery.
Non-viral approaches for gene therapy and therapeutic genome editing across the blood–brain barrier
Authors: Ruosen Xie, Yuyuan Wang, Jacobus C. Burger, Dongdong Li, Min Zhu, Shaoqin Gong
Journal: Med-X (2023)

Abstract The success of brain-targeted gene therapy and therapeutic genome editing hinges on the efficient delivery of biologics bypassing the blood–brain barrier (BBB), which presents a significant challenge in the development of treatments for central nervous system disorders. This is particularly the case for nucleic acids and genome editors that are naturally excluded by the BBB and have poor chemical stability in the bloodstream and poor cellular uptake capability, thereby requiring judiciously designed nanovectors administered systemically for intracellular delivery to brain cells such as neurons. To overcome this obstacle, various strategies for bypassing the BBB have been developed in recent years to deliver biologics to the brain via intravenous administration using non-viral vectors. This review summarizes various brain targeting strategies and recent representative reports on brain-targeted non-viral delivery systems that allow gene therapy and therapeutic genome editing via intravenous administration, and highlights ongoing challenges and future perspectives for systemic delivery of biologics to the brain via non-viral vectors.
MRI-guided robot intervention—current state-of-the-art and new challenges
Authors: Shaoping Huang, Chuqian Lou, Ying Zhou, Zhao He, Xuejun Jin, Yuan Feng, Anzhu Gao, Guang-Zhong Yang
Journal: Med-X (2023)

Abstract Magnetic Resonance Imaging (MRI) is now a widely used modality for providing multimodal, high-quality soft tissue contrast images with good spatiotemporal resolution but without subjecting patients to ionizing radiation. In addition to its diagnostic potential, its future theranostic value lies in its ability to provide MRI-guided robot intervention with combined structural and functional mapping, as well as integrated instrument localization, target recognition, and in situ, in vivo monitoring of the therapeutic efficacy. Areas of current applications include neurosurgery, breast biopsy, cardiovascular intervention, prostate biopsy and radiotherapy. Emerging applications in targeted drug delivery and MRI-guided chemoembolization are also being pursued. Whilst promising progress has been made in recent years, there are still significant basic science research and engineering challenges. This paper provides a comprehensive review of the current state-of-the-art in MRI-guided robot intervention and allied technologies in actuation, sensing, new materials, interventional instruments, and interactive/real-time MRI. Potential future research directions and new clinical developments are also discussed.
US-guided ablation of tumors – where is it used and how did we get there
Authors: Jia-peng Wu, Jie Yu, J. Brian Fowlkes, Ping Liang, Christian Pállson Nolsøe
Journal: Med-X (2023)

Abstract Ablation under ultrasound (US) guidance for the treatment of various tumors in liver, thyroid, prostate, kidney, uterine and many other organs evolved extensively in the past decades. Major ablative techniques, including radiofrequency ablation, microwave ablation, high intensity focused ultrasound, cryoablation, percutaneous ethanol injection, laser ablation and irreversible electroporation, have all been widely applied and ablation is recommended by several guidelines as first-line or alternative therapy e.g. hepatocellular carcinoma in early stage, T1a stage renal cell carcinoma and thyroid nodules. In the current article, we reviewed 2508 articles on tumor ablation under US guidance and present the status of US-guided tumor ablation globally.
Type 17 mucosal-associated invariant T cells contribute to neutrophilic inflammation in patients with nasal polyps
Authors: Xiaoyan Ye, Yachun Li, Bixing Fang, Yizhang Yuan, Danni Feng, Hexin Chen, Jian Li, Qingxiang Meng, Shaobing Xiong, Dongmei Ye, Linyi Jiao, Dehua Chen, Ruchong Chen, Wenbin Lei, Yifang Gao, Chunwei Li
Journal: Journal of Allergy and Clinical Immunology (2023)
Noninvasive and affordable type 2 diabetes screening by deep learning-based risk assessment and detection using ophthalmic images inspired by traditional Chinese medicine
Authors: Zhi Zhang, Han Wang, Lei Chen, Chensi Cao, Tengwen Liu, Ruifang Ren, Ruixing Zhou, Rudan Huang, Dan Hu, Chenxing Zhu, Chong Lu, Yunsheng Xu, Zhaohui Fang, Fuer Lu, Huimin Pan, Yanjin Su, Nanlin Fu, Huixia Zhan, Qin Si, Chenze Bai, Ri Le Ge, Hongmei Cao, Wei Dong, Guohui Yang, Lan Wu, Jiao Guo, Jing Cheng
Journal: Med-X (2023)

Abstract The global prevalence of diabetes is steadily increasing, with a high percentage of patients unaware of their disease status. Screening for diabetes is of great significance in preventive medicine and may benefit from deep learning technology. In traditional Chinese medicine, specific features on the ocular surface have been explored as diagnostic indicators for systemic diseases. Here we explore the feasibility of using features from the entire ocular surface to construct deep learning models for risk assessment and detection of type 2 diabetes (T2DM). We performed an observational, multicenter study using ophthalmic images of the ocular surface to develop a deep convolutional network, OcularSurfaceNet. The deep learning system was trained and validated with a multicenter dataset of 416580 images from 67151 participants and tested independently using an additional 91422 images from 12544 participants, and can be used to identify individuals at high risk of T2DM with areas under the receiver operating characteristic curve (AUROC) of 0.89–0.92 and T2DM with AUROC of 0.70–0.82. Our study demonstrated a qualitative relationship between ocular surface images and T2DM risk level, which provided new insights for the potential utility of ocular surface images in T2DM screening. Overall, our findings suggest that the deep learning framework using ocular surface images can serve as an opportunistic screening toolkit for noninvasive and low-cost large-scale screening of the general population in risk assessment and early identification of T2DM patients.
Efficacy and safety of the siRNA JNJ-73763989 and the capsid assembly modulator JNJ-56136379 (bersacapavir) with nucleos(t)ide analogues for the treatment of chronic hepatitis B virus infection (REEF-1): a multicentre, double-blind, active-controlled, randomised, phase 2b trial
Authors: Man-Fung Yuen, Tarik Asselah, Ira M Jacobson, Maurizia Rossana Brunetto, Harry L A Janssen, Tetsuo Takehara, Jin Lin Hou, Thomas N Kakuda, Tom Lambrecht, Maria Beumont, Ronald Kalmeijer, Carine Guinard-Azadian, Cristiana Mayer, John Jezorwski, Thierry Verbinnen, Oliver Lenz, Umesh Shukla, Michael Biermer, Stefan Bourgeois, Thomas Vanwolleghem, Frederik Nevens, Yves Horsmans, Hans Van Vlierberghe, Ana Catharina Nastri, Marcus Lacerda, Alnoor Ramji, Brian Conway, Carla Coffin, Harry Janssen, Scott Fung, Stephen Shafran, Jin Lin Hou, Jan Sperl, Petr Urbanek, Stanislav Plisek, Vaclav Hejda, Didier Samuel, Karine Lacombe, Fabien Zoulim, Dominique Guyader, Francois Raffi, Tarik Asselah, Marc Bourliere, Marie-Noelle Hilleret, Heiner Wedemeyer, Julian Schulze zur Wiesch, Kathrin Sprinzl, Florian van Boemmel, Gudrun Hilgard, Michael Sabranski, Keikawus Arasteh, Henry LY Chan, Man Fung Yuen, Vincent Ws Wong, Maurizia Rossana Brunetto, Gloria Taliani, Pietro Andreone, Pietro Lampertico, Masayuki Kurosaki, Hiroshi Yatsuhashi, Kei Fujiwara, Tetsuo Takehara, Tomokazu Kawaoka, Yasuhiro Asahina, Hirayuki Enomoto, Kazuhisa Yabushita, Kazuo Notsumata, Koichi Takaguchi, Naoto Kawabe, Naoya Kato, Ogawa Koji, Tadashi Namisaki, Yoshiyuki Suzuki, Jung-Hwan Yoon, SangHoon Ahn, Young-Suk Lim, Seung Woon Paik, Kuang Kiat Kiew, Rosmawati Mohamed, Soek Siam Tan, Yeong Yeh Lee, Maria Hlebowicz, Hanna Berak, Jacek Gasiorowski, Waldemar Halota, Ewa Janczewska, Natalia Geyvandova, Viacheslav Morozov, Alla Andreeva, Denis Gusev, Elena Bessonova, Marina Osipenko, Svetlana Romanova, Natalia Gankina, Olga Sagalova, Tatiana Stepanova, Javier Crespo Garcia, Moises Diago, Fernandez Inmaculada, Jose Luis Calleja, Xavier Forns, Maria Buti, Pisit Tangkijvanich, Tawesak Tanwandee, Teerha Piratvisuth, Apinya Leerapun, Gurdal Yilmaz, Ömer Fehmi Tabak, Ulus Salih Akarca, Murat Akova, Ramazan Idilman, Daniel Forton, David Bell, Kosh Agarwal, Patrick Kennedy, Franco Felizarta, Mark Sulkowski, Ronald Nahass, Sergio Rojter, Ira Jacobson, Kevin Korenblat, Norman Gitlin
Journal: The Lancet. Gastroenterology & hepatology (2023)
Organisational factors associated with hospital costs and patient mortality in the 365 days following hip fracture in England and Wales (REDUCE): a record-linkage cohort study
Authors: Petra Baji, Rita Patel, Andrew Judge, Antony Johansen, Jill Griffin, Tim Chesser, Xavier L Griffin, Muhammad K Javaid, Estela C Barbosa, Yoav Ben-Shlomo, Elsa M R Marques, Celia L Gregson, Rachael Gooberman-Hill, Sarah Drew, Katie Whale, Marianne Bradshaw
Journal: The Lancet Healthy Longevity (2023)

Hip fracture care delivery varies between hospitals, which might explain variations in patient outcomes and health costs. The aim of this study was to identify hospital-level organisational factors associated with long-term patient outcomes and costs after hip fracture.REDUCE was a record-linkage cohort study in which national databases for all patients aged 60 years and older who sustained a hip fracture in England and Wales were linked with hospital metrics from 18 organisational data sources. Multilevel models identified organisational factors associated with the case-mix adjusted primary outcomes: cumulative all-cause mortality, days spent in hospital, and inpatient costs over 365 days after hip fracture.Between April 1, 2016, and March 31, 2019, 178 757 patients with an index hip fracture were identified from 172 hospitals in England and Wales. 126 278 (70·6%) were female, 52 479 (29·4%) were male, and median age was 84 years (IQR 77-89) in England and 83 years (77-89) in Wales. 365 days after hip fracture, 50 354 (28·2%) patients had died. Patients spent a median 21 days (IQR 11-41) in hospital, incurring costs of £14 642 (95% CI 14 600-14 683) per patient, ranging from £10 867 (SD 5880) to £23 188 (17 223) between hospitals. 11 organisational factors were independently associated with mortality, 24 with number of days in hospital, and 25 with inpatient costs. Having all patients assessed by an orthogeriatrician within 72 h of admission was associated with a mean cost saving of £529 (95% CI 148-910) per patient and a lower 365-day mortality (odds ratio 0·85 [95% CI 0·76-0·94]). Consultant orthogeriatrician attendance at clinical governance meetings was associated with cost savings of £356 (95% CI 188-525) and 1·47 fewer days (95% CI 0·89-2·05) in the hospital in the 365 days after hip fracture per patient. The provision of physiotherapy to patients on weekends was associated with a cost saving of £676 (95% CI 67-1285) per patient and with 2·32 fewer days (0·35-4·29) in hospital in the 365 days after hip fracture.Multiple, potentially modifiable hospital-level organisational factors associated with important clinical outcomes and inpatient costs were identified that should inform initiatives to improve the effectiveness and efficiency of hip fracture services.Versus Arthritis.
Empower women to grow
Authors: None The Lancet Planetary Health
Journal: The Lancet Planetary Health (2023)

On 16th of June 2023, during World Day to Combat Desertification and Drought, representatives of the United Nations Convention to Combat Desertification (UNCCD) warned the international community that women and girls in low- and middle-income countries are suffering the greatest burden of drought, land degradation, and desertification. Climate change and intensive, unsustainable land use, combined with legal and socioeconomic inequalities, mean that women, especially in rural and agricultural settings, are the most exposed to food and water scarcity and to forced migration.
Scope and applicability of social–ecological resilience to antimicrobial resistance
Authors: Didier Wernli, Peter Søgaard Jørgensen, E Jane Parmley, Shannon E Majowicz, Irene Lambraki, Carolee A Carson, Melanie Cousins, Tiscar Graells, Patrik J G Henriksson, Anaïs Léger, Stephan Harbarth, Max Troell
Journal: The Lancet Planetary Health (2023)